Inhibition of intracellular Angiotensin II formation blocks high glucose effect on mesangial matrix

High glucose causes increased matrix synthesis by glomerular mesangial cells and angiotensin II (Ang II) has been shown to mediate this effect of glucose. These studies investigate whether inhibition of Ang II formation can block high glucose-induced increase in mesangial matrix. Human mesangial cells were incubated with 25 mM glucose (HG) along with captopril, an ACE inhibitor, to block Ang II formation. In other experiments, cells were nucleofected with siRNA to knockdown angiotensinogen (Agt), the precursor of Ang II, and then exposed to high glucose. Captopril blocked high glucose-induced increase in Ang II levels in the cell media (extracellular) but failed to inhibit it in the cell lysate (intracellular). Moreover, captopril treatment did not block the stimulatory effect of high glucose on TGF-β1 and fibronectin. In contrast, knockdown of the Agt gene prevented high glucose-induced increase in both extracellular and intracellular Ang II levels, and was accompanied by normalization of TGF-β1 and fibronectin. These data suggest that intracellular Ang II may play an important role in the mediation of the high glucose effect on matrix and that ACE inhibitors may not be effective in blocking intracellular Ang II formation in mesangial cells.     

Some aspects of haematology of a common Indian field rat, Rattus rattus arborious (Linn.) in relation to sex and size.

In the present investigation the studies on erythrocyte and leucocyte counts, haemoglobin concentration, haematocrit values, blood biochemistry of protein, glucose and cholesterol, erythrocyte sedimentation rate, pH value, diameter of erythrocyte and clotting time were made in different sex and size (weight group) of an Indian field rat, Rattus rattus arborious. The number of erythrocyte, haemoglobin concentration, haematocrit values were found to be higher in females than the males, while the number of leucocyte was lower in females in comparison to males. In the biochemical estimation the value of protein in females was high while that of the glucose and cholesterol were lower than that of the males. All the above values showed an increasing tendency with the increase in body weight. pH value, diameter of erythrocyte and clotting time were found to be almost constant in rats of different weight groups and different sex.     

Role of L-thyroxine, hydrocortisone and progesterone in regulation of blood volume in a fresh-water air-breathing fish, Clarias batrachus (Linn.).

Effect of hormones on the blood volume of Clarias batrachus were ascertained and it was observed L-thyroxine and progesterone decrease, while hydrocortisone increases the total and relative blood volumes. The ratio of plasma to corpuscular volume is increased by the intraperitoneal injection of L-thyroxine, hydrocortisone and progesterone (higher dose only), thus indicating the regulation of blood volume under the complex control of homeostasis.     

Molecular dynamics and quantum chemistry-based approaches to identify isoform selective HDAC2 inhibitor – a novel target to prevent Alzheimer’s disease

Histone deacetylase 2 (HDAC2) is an emerging target of Alzheimer’s disease. Four featured pharmacophore model (ADRR) with one H-bond acceptor (A), one H-bond donor (D), and two aromatic rings (R) was generated using experimentally reported compounds, ((E-5[3-benzenesulfonamido) phenyl]-N-hydroxypent-2-en-4-ynamide)) and (N’-hydroxy-N-phenyloctanediamide) with IC₅₀ values of 0.16?±?0.11?nM and 62?±?0.15?nM, respectively. Quantum Polarized Ligand Docking and Binding Free Energy calculation was performed for the top three identified leads RH01652, JFD02573, and HTS00800 from HitFinder database. RH01652 (methyl 2-[({5-[(benzoylamino) methyl]-2-thienyl} sulfonyl) amino]-3-(1H-indol-3-yl) propanoate) with docking score (?12.62?kcal/mol) and binding free energy (?75.27?kcal/mol), shows good binding affinity. RH01652 interacts with Gly154, His183, Glu208, and Phe210 with four H-bonds and stabilized by π–π interactions with His146, Tyr209, and Phe210. DFT studies at B3LYP level with 6-31G* basis set for the lead RH01652 reveals low band gap/ΔE (E_HOMO–E_LUMO) of ?0.16?eV, which illustrates good reactivity of the lead. MD simulation studies (40?ns) was performed to confirm the stability of lead binding. Comparative molecular docking studies of the lead RH01652 with class I HDACs (HDAC1, HDAC2, HDAC3, and HDAC8) shows higher binding affinity towards HDAC2. Thus, lead RH01652 could serve as template to design novel and potent inhibitor of HDAC2.     

Role of adiponectin as a modulator of testicular function during aging in mice

The mechanisms by which testicular functions decline with aging remain largely speculative. Our recent finding showed the importance of adiponectin in the regulation of testicular functions, whereas its concentration declines during male infertility. Thus, the aim of present study was to explore the potential role of adiponectin during aging. The changes in adiponectin, adiponectin-receptors, and insulin receptor proteins expression in the testis were evaluated and compared with the testicular parameters, mass, and testosterone level in the mice from early post-natal to late senescence period. Further, the current study has examined the effect of exogenous adiponectin treatment on testicular functions in aged mice. The results showed a significant decline in adiponectin/adiponectin-receptors expression simultaneously with a significant decline in testicular mass, insulin receptor expression and testosterone synthesis in the testis of aged mice. Exogenous treatment of adiponectin to aged mice resulted in marked improvements in testicular mass, histological features (cells proliferation), insulin receptor expression, testicular glucose uptake, anti-oxidative enzymes activity and testosterone synthesis as compared with the control. Based on these findings, it may be concluded that a marked decline in adiponectin synthesis and action results in decreased insulin sensitivity (development of insulin resistance) and increased oxidative stress which consequently suppresses testicular functions during aging. This study further showed that treatment with adiponectin ameliorates reduced testicular functions by enhanced expression of insulin receptor in the testis of senescent mice. It is thus hypothesized that systemic adiponectin treatment could be a promising therapeutic strategy for improvement of testosterone production and sperm counts during aging.     

Studies on blood components of an air-breathing siluroid fish, Heteropneustes fossilis (Bloch) in relation to body weight.

Different haematological parameters have been studied in relation to the body weight of Heteropneustes fossil (Bloch). The erythrocytes and leucocytes number and haemoglobin concentration increases from lower to higher weight groups. The heart weight also increases along with other blood components. With the unit increase in the body weight of this fish, the heart weight, erythrocytes, leucocytes and haemoglobin increase by a fractional power of 0.85700, 0.13480, 0.13215 and 0.22876, respectively. This shows that haemoglobin increases at a higher rate than erythrocyte number. The coefficient of correlation between body weight and erythrocyte (r = 0.70015), leucocytes (r = 0.95861), haemoglobin (r = 0.96615) and heart weight (0.97577) indicate high degree of correlation. The erythrocytes and leucocytes count and haemoglobin concentration per gram body weight is higher in younger fishes and decrease as the animal grows in size. The haematocrit values and mean corpucsular volumes decrease from lower to higher weight groups, whereas mean corpuscular haemoglobin concentration increases with body weight. The erythrocyte cell surface has a decreasing trend from lower to higher weight group. Due to difference in the rate of decrease of greatest and least diameter of erythrocytes, the elliptical shape of R.B.C. which is common in younger animals, becomes circular in higher weight group. The non-granulocytes increase constantly while the percentage of granulocytes decreases from lower to higher weight groups. The lymphocytes constitute the main bulk of all the leucocytes. The total lymphocytes also increase with the body weight. Spindle cells and monocytes are relatively less in numbers. The percentage of eosinophils, basophils and neutrophils also decrease from lower to higher weight groups.     

Insect drift over the northern Arabian sea in early summer

Air borne insects, mostly carried by wind currents, were trapped over the northern Arabian sea (16‡ to 20‡ N; 68‡ to 72‡ E), in the course of cruise No. 111, ORVSAGAR KANYA (March 14 to April 7, 1996). A total of 2,301 insects belonging to 8 different orders, 47 families and 173 species were trapped. Of these, Hymenoptera was represented by the largest number (1082), which was followed by Hemiptera (586), Diptera (552), Coleoptera (51), Neuroptera (10), Trichoptera (03), Lepidoptera (03) and Orthoptera (01). The trapped insects were mostly between 0.6 mm to over 11 mm long. The data was examined for α-diversity as well as for possible correlations between various parameters like the diversity index, size and number of insects trapped on one hand and the distance of the nearest land mass in wind direction, on the other. Deceased.